iScience
·
2023
·Vol. 26
·期 5
·106705-106705
·
IF 5.8
Jiaojiao Tian,Yingying Chen,Tao Jiang,Xueyan Jia,Hui Gong,Xiangning Li
Resin embedding combined with ultra-thin sectioning has been widely used in microscopic and electron imaging to acquire precise structural information of biological tissues. However, the existing embedding method was detrimental to quenchable fluorescent signals of precise structures and pH-insensitive fluorescent dyes. Here, we developed a low-temperature chemical polymerization method named HM20-T to maintain weak signals of various precise structures and to decrease background fluorescence. The fluorescence preservation ratio of green fluorescent protein (GFP) tagged presynaptic elements and tdTomato labeled axons doubled. The HM20-T method was suitable for a variety of fluorescent dyes, such as DyLight 488 conjugated Lycopersicon esculentum lectin. Moreover, the brains also retained immunoreactivity after embedding. In summary, the HM20-T method was suitable for the characterization of multi-color labeled precise structures, which would contribute to the acquisition of complete morphology of various biological tissues and to the investigation of composition and circuit connection in the whole brain.
研究领域:
神经科学
·
分子生物学
·
成像技术
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DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2020
·
IF 2.888
Masumeh Mokhtarpour,Hemayat Shekaari
Thermodynamic properties of novel bio-based deep eutectic solvents (DESs) and their mixture with other solvents is of great importance in extraction and pharmaceutical sciences. In the present study new class of these neoteric sustainable solvents composed of amino acids and lactic acid have been prepared, density and speed of sound data for neat lactic acid/alanine, lactic acid/glycine and lactic acid/histidine and their aqueous mixture have been measured over the entire composition range at T = (298.15, 303.15, 308.15 and 313.15) K. Based on these data, some of the thermodynamic properties including the excess molar volumes ( V E ), apparent molar volume ( V ϕ ), excess isobaric thermal expansion ( α p , m E ), the excess molar isentropic compressibility ( κ E s,m ) and limiting apparent molar expansibility ( ϕ E , 1 0 ) have been calculated. For all of the studied systems above, these important properties have been analysed based on various solute-solvent interactions, occurring between the components of the mixtures. Furthermore, it has been found that all the investigated DESs act as a structure-breaker in water over the whole temperature range using Hepler’s constant. The properties have been correlated by the Redlich-Kister type equations.
研究领域:
化学
·
生物化学
·
制药科学
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DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2022
·
IF 3.119
Yanjuan Peng,Ziteng Wang,Wenhao Jiao,Xinxin Cheng,Jingjing Yang,Yonghong Hu,Li Mi
This article deals with the saturated solubility and solvation behavior of 2-bromo-9-fluorenone in 10 industrial common solvents and three binary mixed solvents by means of experimental and mathematical correlations. Solubility experiments were investigated using the static equilibrium method combined with high-performance liquid chromatography (HPLC) from 278.15 to 323.15 K at atmospheric pressure. The results showed that the maximum and minimum solubility of 2-bromo-9-fluorenone was 0.0526 (mole fraction) in 1,4-dioxane at 323.15 K and 0.0002 (mole fraction) in methanol at 278.15 K, respectively, and the solubility increased with the increase in temperature in all solvents. Furthermore, the solubility data of 2-bromo-9-fluorenone was analyzed using the Apelblat model, the Buchowski–Ksiazaczak λh model in pure solvents, CNIBS/R-K model, and the Jouyban–Acree model in binary solvent mixtures. By error comparison, the Apelblat model and the CNIBS/R-K model can better predict the solubility of 2-bromo-9-fluorenone. In addition, the solvation behavior was illustrated by the KAT-LSER model in pure solvents, and the result shows that the cohesive energy density in the solution is the main factor affecting 2-bromo-9-fluorenone. Therefore, the solubility data is very important for optimizing the extraction process and recrystallizing 2-bromo-9-fluorenone to obtain a higher yield in industry production.
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产品关联
DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2022
·
IF 3.119
Guang Yang,Shaoming Fang,Jianqiang Zhang,Ruijuan Wang,Ruixue Liu,Renjie Xu,Chunjuan Huang
The solubility of 2-amino-3-chloropyrazine (ACPY) in some binary cosolvent mixtures of (methanol, isopropyl alcohol, ethylene glycol (EG), N,N-dimethylformamide (DMF)) plus water and the experimental solubility of 2-amino-3,5-dibromopyrazine (ADPY) in (ethanol + water), (isopropyl alcohol + water), (EG + water), and (PG + water) were all determined by the isothermal saturation method from 278.15 K to 323.15 K at 101.2 kPa. The trend of the system temperature and the change of the solvent partner are both factors that affect the dissolution. As the temperature goes higher, the amount of dissolution follows, but the higher is the water content of the solvent, the less solute will be dissolved. The combination of DMF and water is best for the dissolution of ACPY, and the addition of ethanol to water shows an advantage of dissolving ADPY over other combinations. The experimentally obtained dissolution data were then calculated by using three models for the two miscible solvent systems. For ADPY, RAD and RMSD maximums were 2.63 × 10–2 and 2.10 × 10–5. For ACPY, RAD and RMSD were no greater than 6.55 × 10–2 and 6.83 × 10–4.
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产品关联
DOI
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2020
·
IF 2.888
Zhan-Ping Qiao,Tian Yang,Shu-Zhi Cao,Yu-Feng Tang,Qi-Chao Yang
Solid-liquid equilibria in the ternary systems RbX + CdX 2 + H 2 O (X = Cl, Br) at T = 298.15 K and under 101.3 kPa were investigated by the method of isothermal solution saturation, and the corresponding phase diagrams were constructed. It was found that there were five crystallization regions corresponding to CdCl 2 ·2.5H 2 O, RbCd 2 Cl 5 ·H 2 O, RbCdCl 3 , Rb 4 CdCl 6 and RbCl in the system (RbCl + CdCl 2 + H 2 O). Four crystallization regions corresponding to CdBr 2 ·4H 2 O, RbCdBr 3 , Rb 4 CdBr 6 and RbBr were found in the system (RbBr + CdBr 2 + H 2 O). The new solid compounds RbCdCl 3 , RbCdBr 3 and Rb 4 CdBr 6 were congruently soluble in water, and new double salts RbCd 2 Cl 5 ·H 2 O and Rb 4 CdCl 6 were incongruently soluble in water. The new solid-phase compounds RbCd 2 Cl 5 ·H 2 O, RbCdCl 3 , Rb 4 CdCl 6 , RbCdBr 3 and Rb 4 CdBr 6 were characterized by chemical analysis, XRD and TG-DTG techniques. The standard molar enthalpies of solution of RbCd 2 Cl 5 ·H 2 O, RbCdCl 3 , Rb 4 CdCl 6 , RbCdBr 3 and Rb 4 CdBr 6 in water were measured to be (20.74 ± 0.16) kJ·mol −1 , (28.00 ± 0.39) kJ·mol −1 , (96.56 ± 0.50) kJ·mol −1 , (35.38 ± 0.33) kJ·mol −1 and (110.64 ± 0.62) kJ·mol −1 by microcalorimetry in the condition of infinite dilution, and their standard molar enthalpies of formation were determined to be −(1545.3 ± 0.6) kJ·mol −1 , −(856.5 ± 0.7) kJ·mol −1 , −(2180.1 ± 1.3) kJ·mol −1 , −(727.1 ± 0.7) kJ·mol −1 and −(1920.5 ± 1.3) kJ·mol −1 , respectively.
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高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2017
·
IF 3.648
Jiahong Zhu,Keke Yu,Yugang Zhu,Ruyu Zhu,Fangfang Ye,Ning Song,Yingjie Xu
Three deep eutectic solvents (DESs) were synthesized using choline chloride (ChCl) and phenolic compounds (phenol, p -cresol, and p -chlorophenol) as hydrogen bond donors (HBD) with a molar ratio of 1:2 (ChCl:HBD). Densities ( ρ ), viscosities ( η ), and refractive indices ( n D ) of DESs were measured at T = (293.15 to 333.15) K under atmospheric pressure. Temperature dependence of ρ and η were fitted by empirical equations, and thermal expansion coefficient ( α p ) and activation energy for viscous flow ( E η ) were obtained accordingly. FT-IR spectra of DESs were determined and compared with the corresponding HBDs. Based on physicochemical properties and FT-IR spectra, the influence of electronic effect of substitution group of HBD on hydrogen bond interaction between ChCl and HBD was explored. The results show that the electronic effect of HBD plays an important role on the strength of hydrogen bond interaction of O H ⋯ Cl − of DES. The strong electron-withdrawing property of Cl group of p -chlorophenol can strengthen the hydrogen bond interaction of O H ⋯ Cl − , which leads to higher ρ , η , and n D of DES formed by ChCl and p -chlorophenol. Conversely, CH 3 group of p -cresol exhibits electron-donating effect, resulting in weaker hydrogen bond interaction and lower ρ and n D of DES formed by ChCl and p -cresol. Consequently, the strength of hydrogen bond interaction of O H ⋯ Cl − between ChCl and HBD of DES is as follows: p -chlorophenol > phenol > p -cresol.
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DOI
高影响因子
ACS Nano
·
2020
·
IF 14.588
Jiong Pan,Ping Hu,Yuedong Guo,Junnian Hao,Dalong Ni,Yingying Xu,Qunqun Bao,Heliang Yao,Chenyang Wei,Qingsheng Wu,Jianlin Shi
Cancer immunotherapy shows promising potential in future cancer treatment but unfortunately is clinically unsatisfactory due to the low therapeutic efficacy and the possible severe immunotoxicity. Here we show a combined magnetic hyperthermia therapy (MHT) and checkpoint blockade immunotherapy for both primary tumor ablation and mimetic metastatic tumor inhibition. Monodispersed, high-performance superparamagnetic CoFe2O4@MnFe2O4 nanoparticles were synthesized and used for effective MHT-induced thermal ablation of primary tumors. Simultaneously, numerous tumor-associated antigens were produced to promote the maturation and activation of dendritic cells (DCs) and cytotoxic T cells for effective immunotherapy of distant mimetic metastatic tumors in a tumor-bearing mice model. The combined MHT and checkpoint blockade immunotherapy demonstrate the great potentials in the fight against both primary and metastatic tumors.
研究领域:
肿瘤学
·
纳米技术
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR CELL
·
2019
·
IF 14.548
Peng Wu,Tongtong Zhang,Baoyu Liu,Panyu Fei,Lei Cui,Rui Qin,Huaying Zhu,Danmei Yao,Ryan J. Martinez,Wei Hu,Chenyi An,Yong Zhang,Junwei Liu,Jiawei Shi,Juan Fan,Weiwei Yin,Jie Sun,Chun Zhou,Xun Zeng,Chenqi Xu,Jianan Wang,Brian D. Evavold,Cheng Zhu,Wei Chen,Jizhong Lou
Summary TCRs recognize cognate pMHCs to initiate T cell signaling and adaptive immunity. Mechanical force strengthens TCR-pMHC interactions to elicit agonist-specific catch bonds to trigger TCR signaling, but the underlying dynamic structural mechanism is unclear. We combined steered molecular dynamics (SMD) simulation, single-molecule biophysical approaches, and functional assays to collectively demonstrate that mechanical force induces conformational changes in pMHCs to enhance pre-existing contacts and activates new interactions at the TCR-pMHC binding interface to resist bond dissociation under force, resulting in TCR-pMHC catch bonds and T cell activation. Intriguingly, cancer-associated somatic mutations in HLA-A2 that may restrict these conformational changes suppressed TCR-pMHC catch bonds. Structural analysis also indicated that HLA polymorphism might alter the equilibrium of these conformational changes. Our findings not only reveal critical roles of force-induced conformational changes in pMHCs for activating TCR-pMHC catch bonds but also have implications for T cell-based immunotherapy.
研究领域:
免疫学
·
生物物理学
·
分子生物学
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DOI
PubMed
高影响因子
Cell Death Discovery
·
2024
·Vol. 10
·期 1
·1-14
·
IF 6.1
Sun Bao-Ye,Wang Zhu-Tao,Chen Ke-Zhu,Song Yang,Wu Jing-Fang,Zhang Dai,Sun Guo-Qiang,Zhou Jian,Fan Jia,Hu Bo,Yi Yong,Qiu Shuang-Jian
Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8 + T cell infiltration and better prognoses in ICC patients. Mechanistically, β-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, β-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic β-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or β-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
癌症免疫治疗
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DOI
高影响因子
Cell Reports
·
2023
·Vol. 42
·期 11
·113388-113388
·
IF 8.8
Song J,Liu Y,Yin Y,Wang H,Zhang X,Li Y,Zhao X,Zhang G,Meng X,Jin Y,Lu D
Cancer evades host immune surveillance by virtue of poor immunogenicity. Here, we report an immune suppressor, designated as PTIR1, that acts as a promotor of tumor immune resistance. PTIR1 is selectively induced in human cancers via alternative splicing of DDX58 (RIG-I), and its induction is closely related to poor outcome in patients with cancer. Through blocking the recruitment of leukocytes, PTIR1 facilitates cancer immune escape and tumor-intrinsic resistance to immunotherapeutic treatments. Unlike RIG-I, PTIR1 is capable of binding to the C terminus of UCHL5 and activates its ubiquitinating function, which in turn inhibits immunoproteasome activity and limits neoantigen processing and presentation, consequently blocking T cell recognition and attack against cancer. Moreover, we find that the adenosine deaminase ADAR1 induces A-to-I RNA editing on DDX58 transcript, thus triggering PTIR1 production. Collectively, our data uncover the immunosuppressive role of PTIR1 in tumorigenesis and propose that ADAR1-PTIR1-UCHL5 signaling is a potential cancer immunotherapeutic target.
研究领域:
癌症生物学
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免疫学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Guanghui Hou,Junmin Qian,Min Guo,Weijun Xu,Jinlei Wang,Yaping Wang,Aili Suo
Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H 2 O 2 to O 2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4 + and CD8 + T cells . Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment.
研究领域:
肿瘤学
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纳米技术
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免疫学
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药学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Simiao Qiao,Xingpan Lian,Mengfan Yue,Qin Zhang,Zhifeng Wei,Li Chen,Yufeng Xia,Yue Dai
Previously, we reported that oral administration of madecassoside, the main active triterpene in Centella asiatica L., exerted anti-arthritis effect by inducing the generation of regulatory T (Treg) cells in small intestine. This study investigates the action site and mechanism of madecassoside to induce Treg cells. In collagen-induced arthritis (CIA) of rats, oral administration of madecassoside significantly alleviated arthritis symptoms, but its main metabolite madecassic acid did not, suggesting that madecassoside functions in the parent form. Madecassoside was shown to increase the number of Treg cells and promote the expression of Foxp3 and IL-10 in rat ileum rather than duodenum and jejunum, as detected using the immunohistochemistry assay and quantitative PCR assay, respectively. Unexpectedly, madecassoside was absent of significant effect on in vitro Treg cell differentiation and the expression of Foxp3 and IL-10. A combined use of broad-spectrum antibiotics resulted in significant reduction of the anti-arthritis effect of madecassoside in CIA rats. The 16S rRNA gene sequence showed that madecassoside could reverse the changes of gut microbiota under arthritis condition, and enrich several bacteria such as Lachnospiraceae, Butyricicoccus, Faecalibacterium, Butyricicoccus pullicaecorum and so on. GC-MS assay showed that madecassoside elevated the levels of acetic acid and butyric acid, but not other short chain fatty acids (SCFAs) in the cecum contents of CIA rats. Butyric acid rather than acetic acid could induce the in vitro differentiation of Treg cells and the expression of Foxp3 and IL-10. Accordingly, when madecassoside was co-administered with heptanoyl CoA, the competitive inhibitor of butyrate synthase, its effect on butyric acid production, Treg cell proportion and arthritis nearly disappeared. These findings indicate that oral madecassoside induces the generation of Treg cells and therefore displays anti-arthritis effect in the parent form but not metabolites, and the ileum is the main action site. The mechanism of madecassoside can be summarized as: expansion of the richness of butyrate-producing bacteria-up-regulation of intestinal butyrate level-induction of Treg cell differentiation and IL-10 expression.
研究领域:
免疫学
·
药理学
·
微生物学
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
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